Device and method for attaracting diseased cells and foreign substances

ABSTRACT

An implantable device for attracting diseased cells or foreign substances circulating within bodily fluid channels is disclosed. The device comprises a frame, an attachment means for maintaining the frame in a localized position in a body vessel, and at least one attractant on the frame, where the attractant is capable of attracting a diseased cell or a foreign substance. The device may also include a therapeutic agent The device may be used for diagnosis, disease containment or treatment. The device may also be used for attracting and localized treatment of diseased cells and foreign substances.

FIELD OF THE INVENTION

The invention generally relates to the attraction of cells or virusescirculating through blood vessels, lymph channels, and spinal fluidchannels for localized therapy, disease containment, or diagnosis.

BACKGROUND OF THE INVENTION

Disease may spread through a body via fluid channels. Disease may comein many forms from foreign substances such as viruses, bacteria,parasites and the like, to diseased cells, such as cancerous cells,infected or damaged cells. Once in fluid channels, such as the vascularsystem, lymph system or spinal fluid channels, these diseases may beable to circulate in a body. For example, most cancer deaths are causedby metastasis rather than primary tumours. The delivery of circulatingcancer cells to secondary sites is generally regulated by bodily fluidflow and the molecular interaction between the cancer cells and the neworgan environment.

A body has natural means to fight disease. White blood cells, calledleucocytes, circulate in the vascular and lymphatic systems, locatingand attacking foreign substance and diseased cells, as part of a body'simmune response. Occasionally, the response is insufficient to destroythe foreign substances, which may take hold elsewhere in the body andproliferate.

A variety of therapeutic agents may be used. For example, in the case ofcancer, chemotherapy drugs and ionizing radiation may be used to weakenor destroy cancerous cells. Two common chemotherapy administrationoptions are: system-wide doses delivered intravenously, which targettumours and circulating cancer cells, and localized treatment of solidtumours. These therapeutic agents typically have negative side effects,such as weakening a body's immune system and/or destroying healthy cellsalong with cancerous cells. Cancer patients undergoing system-widechemotherapy treatment typically have their white blood cell countdiminished.

Similarly, viruses are infectious agents that proliferate within cells.For most animal viruses, proliferation commences with attachment to ahost cell, mediated by viral attachment proteins that recognizes andinteract with proteins, called receptors, on a suitable host cell. Onceviral components are inside the host cell, viral replication occurs.Certain viruses may circulate within the body until a suitable host cellhaving an appropriate receptor is found, whereupon the virus mayproliferate.

Bacteria may also circulate within a body. Upon finding a suitableenvironment and under appropriate conditions, bacteria may reproducerapidly and in some cases, produce damaging toxins and creating aninfection.

Treatments with anti-viral and antibiotic agents are often system-wideand hence, non-specific, although some localized external applicationsare available. Biotherapeutics, especially small molecule proteins, maybe used for more localized treatments but tend to have a limitedhalf-life, or effective drug releasing time span, within the body.

Accordingly, there is a need for a means to facilitate the localizationof diseased cells and foreign substances in vivo. Such means may be usedfor disease containment in vivo, for facilitating diagnosis, forfacilitating localized application of therapeutic agents, or the like.

SUMMARY OF THE INVENTION

The present invention is directed to an implantable device suitable foruse in attracting diseased cells or foreign substances such as viruses,bacteria, parasites, other microbes, and the like (hereaftercollectively “foreign substances”).

Accordingly, in an aspect of the present invention; there is provided aframe, attachment means for maintaining the frame in a localizedposition in a body vessel, and at least one attractant on the frame,wherein the attractant is capable of attracting a diseased cell orforeign substance within proximity to the frame. In some embodiments,the attractant is able to capture diseased cells or foreign substances,including by binding, electrical interaction, magnetic interaction,fusion, or the like.

A therapeutic agent may also be provided on the frame, the agent adaptedto degrade cells or foreign substances attracted to the frame. The term“degrade” includes any degree of damage or destruction, or to renderless operable, including by endocytosis or dissolution, or the like.

The device may be deployed in any body, mammalian or otherwise, havingfluid channels.

The device may be employed to concentrate or capture circulating cellsor foreign substances in proximity to a frame placed in a specifiedlocation for diagnosis, disease containment, or treatment. The devicemay be used on a wide variety of diseases, including viral, bacterial orparasitic infection or the like. It may be used to reduce or preventmetastasis by capturing cancer cells as they circulate in the body andpreferably before they migrate to and invade distant organs.

In an embodiment, the frame comprises a radially stiff ring. This ringmay also be magnetic.

In an embodiment, the attractant may be bound with endothelial cells,other cells, or agonist equivalents, thereby providing an environmentfor circulating cells or foreign substances to invade. The attractantmay be physically separated from body vessels by the device or membersor membranes provided on the device.

The device may be used to trigger a body's natural defenses, such asleukocytes (white blood cells), or may incorporate additionaltherapeutic agents to degrade diseased cells or foreign substances.

A highly localized dose of minute quantities of chemotherapy orbrachytherapy may be applied to attracted circulating cancer cells,resulting in minimal side effects to healthy tissue.

An object of the disclosed invention is to provide a highly localizedtreatment of circulating cancer cells or other diseased cells or foreignsubstances. Localized micro-chemotherapy to treat metastasis withminimal side effects is not currently available.

The foregoing summarizes the principal features of the invention andsome of its optional aspects. The invention may be further understood bythe description of the preferred embodiments, in conjunction with thedrawings, which follow.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings illustrate presently preferred embodiments ofthe invention and, together with the description that follows, serve toexplain the principles of the invention.

FIG. 1A depicts a perspective view of an embodiment of the inventiondeployed in a blood vessel.

FIG. 1B depicts a perspective view of another embodiment of theinvention deployed in a blood vessel.

FIG. 2A depicts a preferred embodiment of the invention comprised of amagnetic ring.

FIGS. 2A, 2B, 2C, and 2D depict a sequence where the preferredembodiment is supplied with attractant substances and therapeutic agentsin vivo, and captures and treats circulating cancer cells.

FIG. 3 depicts front view and side view of an embodiment of theinvention comprised of an open ended ring with a member extendingradially within the bodily fluid vessel.

FIGS. 4A and 4B depict an embodiment of the invention having amechanical means to destroy captured cells, the means activated by anexternal energy source.

DESCRIPTION OF THE PREFERRED EMBODIMENT

Reference will now be made in detail to various suitable embodiments ofthe invention as illustrated in the accompanying drawings. It will beunderstood that this description is exemplary and is to assist inunderstanding the invention and the principles of operation.

Referring to FIG. 1, an implantable device is provided for use inattracting diseased cells or foreign substances such as viruses,bacteria, fungi, parasites, microbes, or the like. The implantabledevice includes a frame (1) deployed within a patient's blood vessel(2). The frame (1) secures the device to the bodily fluid vessel at aselected location, and binds to it an attractant and a therapeuticagent. Circulating cancer cells (4) are migrating through the bloodvessel.

As depicted in FIG. 1A, the frame (1) is in the form of a single ringthat extends around the circumference of the bodily fluid vessel, suchas an artery or vein, a lymphatic vessel and the like. The frame (1) issized and shaped to frictionally contact the vessel to maintain aposition and has bound to it an attractant and a therapeutic agent.

Alternatively, the frame (1) may be in the form of an open-ended ring, aplurality of rings joined with axial members such as depicted in FIG.1B, a plurality of rings and axial members or struts in a knitted,zig-zag, open cell, closed cell, helical, or other pattern. As a furtheralternative, the frame may be in the form of a simple plug, sphere,pellet, or cylindrical shape.

Instead of frictional contact, the frame (1) may alternatively beembedded into a wall of a bodily fluid vessel with a portion of thedevice exposed to the bodily fluids or be provided outside a vessel withportions extending through a vessel wall for exposure to bodily fluids.Other means for maintaining the frame at a selected location in a vesselare contemplated.

The frame (1) may be provided with members or membranes that extend downthe bodily fluid vessel. The frame may consist of concentric rings orincorporate members that extend axially within the bodily fluid vessel,or extend radially inwards towards the centre of the vessel. FIG. 3depicts another embodiment, comprised of a single ring (1), with amember (8) that extends radially inwards. Members may link opposingsides of the frame radially across the vessel.

Members extending radially inward helps to extend the therapeutic lifeof the device. A few weeks after implanting, the bodily fluid vessellining, the endothelium, may grow over the perimeter surface of theframe, and so the portions of the device extending radially inward willremain exposed to the bodily fluid flow and circulating diseased cellsor foreign substances.

Members extending axially down bodily fluid vessels helps to extend thetherapeutic range of the device, and permit treatment with fewer devicesimplanted in a patient.

The frame may be flexible or rigid. Members or membranes attached to theframe may be flexible or rigid. The frame may be made of a wide varietyof materials: for example, surgical-grade metal, plastic, ceramic,natural fibres, or a combination of materials, and may be formed in avariety of sizes. Struts may typically range from 0.1 to 4 mm inthickness, and the overall length of the device may typically range from1 to 20 mm. The device dimensions may be lesser or greater than thetypical range.

Alternatively, the frame may be made of a biodegradable material thatover a period of months or years is absorbed and disappears. This wouldavoid long-term health and safety concerns associated with metallic orother non-biodegradable implants.

As a further alternative, the frame may be coated with bioactivetreatments to improve device performance. Most materials can absorb aheparin type coating that reduces thrombus formation on blood-contactingdevices. This form of coating can be used with other molecules toenhance cell attachment. Such a treatment may be applied by dip coating,flow-through, or spraying.

The frame or a portion of the frame may be magnetic. This includes theincorporation of at least one magnetic component, for example, a ferrousparticle. FIG. 2A, depicts a presently preferred embodiment of thedevice comprised of a magnetized ring.

The frame may also incorporate physical features, surface treatments,markings, or coatings to enhance its visibility to imaging systems.Struts, or markings scribed into the frame surface, may be spaced tocorrespond to typical diagnostic ultrasound wavelengths in order toenhance the echogenicity of the device for ultrasound imaging. Thedevice may elute MRI, X-ray, CT scan, ultrasound, or fluoroscopiccontrast agents to enhance its visibility to those imaging systems.

Bound to the frame (1) is an attractant comprising one or more means toattract circulating cells or foreign substances through physical,chemical, biological, magnetic, electrical, or like means. Preferably,the attractant is able to capture or otherwise concentrate these cellsor foreign substances proximate to the frame (1). Generally, theattractant is specific to a type of cell, a foreign substance, or arelated group thereof.

Some substances have been found to attract cancer cells. For example,chemokines are a class of inflammatory induced, secreted proteins withthe ability to attract and activate circulating leukocytes (white bloodcells) and stem cells to home in on particular organs. Chemokines inducewhite blood cells to migrate towards them and to adhere to theendothelial cells lining blood vessels.

Studies have demonstrated that large quantities of chernokines releasedfrom certain organs also attract circulating cancer cells to invade.

Additionally, agonist drugs have been developed to mimic chemokines, tostimulate physiological activity at cell receptors normally stimulatedby naturally occurring substances. Companies such as ChemokineTherapeutics design peptide analogs and peptidomimetics.

The attractant may be natural, i.e. produced by a body, such aschemokine proteins, neurotransmitters, viral host cell receptorproteins, or other natural receptors, and extracted for use. Theattractant may be agonist drugs or chemical or biochemical formulationsdeveloped to simulate physiological activity at cell receptors, such aschemokine agonists which mimic chemokine proteins. Synthetic constructsmay also be used. A combination of natural substances and/or agonistdrugs and/or chemical or biochemical formulations or the like may beused.

The attractant may be coated, bound, combined or the like, withsubstances such as polymers in order to protect the attractantsubstances within the body and extend their time-release over prolongedperiods.

Additionally, or alternatively, the attractant may be bound with othersubstances or components to provide a suitable environment for capturingcirculating cells or encouraging foreign substances to invade. Theinvasive environment may, for example, consist of endothelial cells ortheir agonist equivalent, other cells, cellular by-products constructsother biotherapeutics or chemicals. Alternatively, these components maybe directly deposited on, or otherwise contained on, the frame. Thecomposition of the attractant and the invasive environment compounds maybe formulated to capture specific types of diseased cells or foreignsubstances.

The frame (1) may elute the attractant and/or other drugs to aidtreatment, improve biocompatibility, or enhance the external imaging ofthe device. Drug elution may be accomplished through coating the frame(1) with one or more attractant that leaches into the bodily fluidvessel or coating the frame (1) with attractant(s) imbedded in a thinpolymer for time-release.

Another drug-elution method includes imbed drugs within a biodegradableframe or body. As the exterior of the frame is absorbed and disappears,drugs are eluted in a time-release manner.

Alternatively, the frame (1) may be formed with receptacles for storingquantities of attractant, which may be released in a time-releasedmanner. Alternatively, there may be provided a containment that isactivated on demand by an external energy source such as therapeuticultrasound to release the attractant. FIG. 1B depicts an embodimentcomprised of a frame (1) comprised of a plurality of rings, axialmembers, and a receptacle (3), deployed within a patient's blood vessel(2). The receptacle (3) contains and continually elutes a substance (notdepicted) to attract and bind circulating cells or foreign substances.

Alternatively, the frame (1) may be embedded into a wall of a bodilyfluid vessel with a portion of the device exposed to the bodily fluids,and the portions extending through a vessel wall may be comprised of orconnected to receptacles for storing quantities of attractant.

Additionally, or alternatively, the attractant may be bound with ferrousparticles, if magnetic means are used, to bind the attractant to theframe. The ferrous particles may be iron oxide as is used withcommercially available magnetic cell separating equipment.

Additionally, the attractant may comprise an electronic componentutilizing electrical properties for attraction.

Accordingly, it is to be understood that the concept of an attractant“on” or “bound to” a frame includes circumstances where the attractantis not physically “on” the frame and contemplates circumstance where theattractant is otherwise proximately connected to the frame, whether by aphysical, magnetic, electrical or chemical connection.

An effective amount of attractant is to be used so as to manifestdesired attraction properties. This amount would likely be in the orderof micrograms, the desired quantity to be confirmed through routinetrials.

The frame (1) may incorporate additional physical features, surfacetreatments, or coatings to enhance the capture of circulating cells,viruses or other foreign substances, or the like. The physical geometryof the device or a portion thereof, may be shaped and/or coated to mimicthe physiology of organs, bone, or other tissues.

For example, the frame (1) may incorporate gold nanoparticles, whichabsorb laser light more thoroughly than other materials, and hencepermit laser-assisted diagnostic imaging or laser ablation of capturedcells or viruses.

Alternatively, the frame (1) may be formed of a plurality of componentsthat are not physically connected but are proximately arranged in orderto permit interaction.

Depending on the application, the circulating cells or foreignsubstances may localized, for example, concentrated in proximity to theframe or be captured onto the frame, for example, by binding, magneticattraction, chemical interaction, electrical attraction or the like. Thelocalized cells or foreign substances may be extracted for diagnosticpurposes, retained in the location to facilitate disease containment, orfor other purposes.

As depicted in FIG. 1, bound to the frame (1) is a therapeutic agent todegrade cells or foreign substances. As set out above, “degrade”includes any degree of damage, destruction, weakening or otherwiserender less operable including by endocytosis or dissolution. Thetherapeutic agent may be an organic or inorganic compound, an ionizingradiation source, a laser source, a mechanical means to degrade, or acombination of different therapeutic agents. Alternatively, thetherapeutic agent may comprise a therapeutic attractant, such as anantigen, a foreign chemical, lymphokines, or the like, to attractvarious immune system cells for a localized immune responsetherapeutically suitable for cells or foreign substances attracted tothe frame. It is to be appreciated that, where lymphokines are desiredto be used, an attractant suitable to attract the desired lymphokines tothe device together with means to stimulate the lymphokine to attack thecells or foreign substances may be required. A plurality of therapeuticagents may also be used.

Comparable to the attractant, the therapeutic agent may be eluted fromthe frame (1). Elution may be accomplished through coating the frame (1)with one or more therapeutic agents that leaches into the fluid vesselor by coating the frame (1) with an agent(s) imbedded in a thin polymerfor time-release. Alternatively, the therapeutic agent may be imbeddedwithin a biodegradable frame. As the exterior of the frame is absorbedand disappears, drugs are eluted in a time-release manner.

Alternatively, the frame (1) may be formed with receptacles for storingquantities of therapeutic agent, which may be released into a vessel ina time-released manner. Alternatively, there may be provided acompartment or orifice that is activated on demand by an external energysource such as therapeutic ultrasound.

Alternatively, the frame (1) may be embedded into a wall of a bodilyfluid vessel with a portion of the device exposed to the bodily fluids,and the portions extending through a vessel wall may be comprised of orconnected to receptacles for storing quantities of therapeutic agents

The therapeutic agent(s) may also be bound with or to a ferrous or othermagnetic particle, if magnetic means are used, to bind the therapeuticagent to the frame.

Where the therapeutic agent is an ionizing radiation source, alphaemitting isotopes may be used to degrade or destroy the captureddiseased cells or viruses, notwithstanding its ordinarily limitedability to penetrate tissue (ie. a cell width). Close proximity may beachieved for a highly localized treatment with minimal damage to healthytissue.

Alternatively, a laser or other high intensity source, acoustic sourceor electrical current or discharge, may be used to ablate or damageattracted cells or foreign substances.

Accordingly, it is to be understood that the concept of a therapeuticagent “on” or in association with a frame includes circumstances wherethe agent is not physically “on” the frame and contemplatescircumstances where the therapeutic agent is otherwise proximatelyconnected to the frame, whether by a physical, magnetic, electrical orchemical connection, or is applied onto or proximate to the frame,including by radiation thereon.

The treatments may be repeated or extended through replenishing thesupply of the attractant substance(s) and/or the therapeutic agent(s),as the case may be. This will permit the attending physicians orveterinarians, or the like, to tailor the treatments to a patient'sspecific needs.

The frame may also form a physical barrier between the attractantsubstance and the patient's tissue. Therefore, the circulating diseasedcells or viruses may invade the attractant substance, for a period oftime before the therapeutic agent is applied, and not invade the patient

As mentioned, the device incorporated into vessels may continually elutesubstance(s), or may release substance(s) upon activation by an externalenergy source such as ultrasonic energy. Repeat treatments may be donethrough means such as intravenous or intra-arterial injection, with abiological, chemical, magnetic, electrical, or other physical means tobind the attractant substance(s), therapeutic Agent(s) or other drugs tothe device.

An effective amount of therapeutic agent is employed, where the agent isa chemical, including drugs. In certain applications, for example, wherecirculating cancer cells have been attracted and are present in thelocal area in sufficient concentrations, a highly localized delivery ofminute quantities of therapeutic agent(s) such as chemotherapy orbrachytherapy may be sufficient. This will result in far less negativeside effects to the patient than is common with most system-widechemotherapy treatments.

The implantable device is generally deployed in bodily fluid vessels,for example, vascular vessels, lymphatic vessels, spinal vessels, or thelike, where circulating diseased cells or viruses are known orsuspected.

The device may be deployed within the bodily fluid vessel using avariety of means, including catheter, needle delivery, and manualplacement in conjunction with surgery.

The device may be deployed as stents are deployed, using guide wires andangioplasty balloon catheters. The balloons come in a wide range oflengths and diameters, and are made from a variety of materials. Theballoon portion of a catheter is inflated to expand the device radiallyoutwardly into contact with the bodily fluid vessel wall, whereupon thedevice undergoes plastic deformation and remains in an expanded state ata fixed position within the bodily fluid vessel.

The device may be deployed as self-expanding stents are deployed, usingcatheters but no balloon. Thermal memory stents are deployed softenedand compressed at a low temperature and return to their original shape,exerting a mild, continuous pressure on the bodily fluid vessel wall.

The device may be delivered via needle or probe, and may pierce thebodily fluid vessel to have a portion of the device exposed to thecirculating diseased cells or viruses and a portion of the device usedto anchor it in position.

Surgical placement of the device may be particularly advantageous tocancer treatment, as difficult to section tumours may be inadvertentlyset in circulation through the body through the surgical procedureitself.

A hybrid device, which accomplishes the aforementioned and in additionperforms the function of a vascular stent, to help keep constrictedblood vessels open, may also be used.

The implantable device may be used individually within a patient or aplurality may be used. A plurality of devices may or not be physicallyjoined, some of which may contain one or more attractants, some of whichmay contain one or more therapeutic agents, and some of which maycontain both one or more attractants to attract and capture circulatingcells or viruses and therapeutic agent(s)

In the case of a patient diagnosed with metastasized cancer, the healthcare personnel may follow a treatment regime such as:

-   -   cycles of system-wide chemotherapy with external beam radiation        or surgery or both    -   implant the device, or a plurality of the devices, within the        body along confirmed or suspected routes of cancer cell        circulation    -   use the device to capture and treat circulating cancer cells    -   replenish the attractant to attract and bind the circulating        cancer cells and the therapeutic agent through intravenous        injection as required for repeat treatments

The device can also be used to diagnose and stage other treatments byproviding an indication of the quantity of captured cells using imagingsystems and/or by retrieving a biopsy sample.

The disclosed device utilizes aspects of existing technology andtechniques:

-   -   Design and deployment techniques for stent like devices        implanted within bodily fluid vessels    -   Biotherapeutics such as chemokines and drug agonists such as        chemokine mimics which attract and bind diseased cells    -   Procedures to protect and prolong the dosage time of        biotherapeutics in vivo    -   Magnetic separation of targeted cells which bind to receptor        cells bound to ferrous particles    -   Delivery of medicaments to specific blood vessels using        intravenous or intra-arterial injection, needles, PortaCath™        type sheaths for repeat injection and other means    -   External energy sources activating medicaments at a depth within        a patient

Embodiments and their operation may be illustrated by the followingexamples.

EXAMPLE 1

In the embodiment of the device as shown in FIG. 1A, the frame iscomprised of 316L stainless steel, laser cut, and polished. Its surfacehas been modified to enhance biocompatibility through a gas plasmatreatment. The frame is coated with an attractant and a therapeuticagent

EXAMPLE 2

FIGS. 2A, 2B, 2C, and 2D depict a sequence whereby the embodiment issupplied with attractant and therapeutic agents in vivo, and capturesand treats circulating cancer cells.

FIG. 2A depicts an embodiment of the device (1) comprised of a magneticring deployed within a patient's blood vessel (2). The device is beingreplenished via intravenous injection (5) with an attractant to attractcirculating cancer cells (6). This attractant (6) consists of an agonistdrug (to mimic chemokine proteins), bound with ferrous particles, andwithin a protective polymer that extends the attractant drug releaseover a prolonged period of time.

FIG. 2B depicts the attractant circulating cells (6) bound to the device(1) by magnetic force. Circulating cancer cells (4) are migrating downthe blood vessel, attracted to the substance (6). The substance (6) mayalso attract circulating white blood cells (not depicted).

FIG. 2C depicts the circulating cancer cells (4) bound to the attractantsubstance (6) and captured by the device (1). A therapeutic agent (7) isbeing injected intravenously (5). The therapeutic agent (7) consists offerrous microparticles coated with a minute quantity of a chemotherapydrug.

The attractant and/or therapeutic agent ferrous particle may also bemagnetized, at the opposite polarity as the device, to enhance binding

FIG. 2D depicts the therapeutic agent (7) bound to the device (1) bymagnetic force. The therapeutic agent (7) elutes the chemotherapy drug,destroying or degrading the captured cancer cells (4). White blood cells(not depicted) may also exert a therapeutic effect on the capturedcancer cells (4). The destroyed cancer cells (4), therapeutic agent (7),and attractant substance (6) break down over time, leaving only ferrousmicroparticles attached to the device (1).

EXAMPLE 3

The device may alternatively incorporate a mechanical means to destroyor otherwise degrade captured cells. This would avoid the need tointroduce therapeutic substances into the patient and would enable thedestruction of captured cells to be done repeatedly as required. Asdepicted in FIG. 4A, the device (1) features a member (9) consisting ofa cantilevered beam positioned over a portion of the surface of thedevice where the attractant is bound (10).

FIG. 4B depicts the device (1), with a mechanical means to destroy ordegrade captured cells, deployed within a blood vessel (2). Oncediseased cells have been attracted to and captured by the device, themember (9) can be set in motion under an external energy source (11) toimpact upon and destroy or degrade the captured cells. The externalenergy source may be ultrasonic, magnetic or other transcutaneous energydelivery means. The cantilevered beam member (9) may have a specificgeometry such that its harmonic frequency corresponds to a set frequencyof a particular ultrasound and the ultrasound energy sets it in resonantvibration.

The foregoing has constituted a description of specific embodimentsshowing how the invention may be applied and put into use. Theseembodiments are only exemplary. The invention in its broadest, and morespecific aspects, is further described and defined in the claims whichnow follow.

These claims, and the language used therein, are to be understood interms of the variants of the invention that have been described. Theyare not to be restricted to such variants, but are to be read ascovering the full scope of the invention as is implicit within theinvention and the disclosure that has been provided herein.

1-55. (canceled)
 56. An implantable device for attracting circulatingcells or foreign substances comprising: a frame configured forattachment to a localized position in a body vessel, and at least oneattractant on the frame, wherein the attractant is capable of attractinga diseased cell or a foreign substance.
 57. An implantable device ofclaim 56, wherein the frame comprises a member for receiving theattractant.
 58. An implantable device of claim 57, wherein the memberforms a physical barrier between a cell lining a fluid vessel and theattractant.
 59. An implantable device according claim 56, wherein theframe comprises magnetic components.
 60. An implantable device accordingto claim 56, further including one or more of: an endothelial cell; anagonist equivalent of an endothelial cell, a host cell, an organ cell,osseous tissue a biotherapeutic, or a chemical, wherein an environmentsuitable for cell or foreign substance proliferation is created.
 61. Animplantable device according to claim 56, wherein the device or aportion of the device is shaped and/or coated to mimic the physiology ofbody organs.
 62. An implantable device according to claim 56, whereinthe device or a portion of the device has been modified to enhance itsvisibility to imaging systems including ultrasound, MRI, X-ray and CTsystems.
 63. An implantable device according to claim 56, wherein theattractant comprises one or more of: a chemokine protein, a viral hostcell receptor proteins, an agonist chemical for stimulatingphysiological activity at a cell receptor, a chemokine agonist, abacterial toxin, a foreign chemical substance, and a combination of anyone of (a) to (f) and, optionally, wherein the attractant is incombination with a protective substance for protecting the attractantand for extending release.
 64. An implantable device according to claim63, wherein the protective substance is a polymer.
 65. An implantabledevice according to claim 63, wherein the attractant includes a magneticcomponent, including a ferrous particle.
 66. An implantable deviceaccording to claim 56, further including a container for containing anddispensing the attractant, and optionally, wherein said containmentmeans dispenses attractant upon activation by an external energy source,said energy source including ultrasonic energy.
 67. An implantabledevice according to claim 66, further including an attractantreplenisher.
 68. An implantable device according to claim 56 furtherincluding a therapeutic agent.
 69. An implantable device according toclaim 68, wherein the therapeutic agent comprises a chemical, amedicament, a chemotherapeutic medicament, an ionizing radiation source,and/or a mechanical agent.
 70. An implantable device according to claim69 wherein the mechanical agent comprises a cantilevered beamactivatable vibrationally upon application of ultrasound at a resonantfrequency.
 71. An implantable device according to claim 69 wherein themechanical agent includes an external energy source, includingultrasound, magnetism, or electricity.
 72. An implantable deviceaccording to claim 68 wherein the therapeutic agent comprises an immuneresponse stimulator, preferably, including an effective amount of anantigen, an interferon, an chemokine, a lymphokine, or a foreignsubstance.
 73. An implantable device according to claim 68, wherein thetherapeutic agent includes a magnetic component, including a ferrousparticle.
 74. An implantable device according to claim 68, furtherincluding a container for containing and dispensing the therapeuticagent, and optionally, wherein the container dispenses therapeutic agentupon activation by an external energy source such as ultrasonic energy.75. An implantable device according to claim 68, further including atherapeutic agent replenisher.
 76. A method of using the implantabledevice according to claim 56 as a cellular attractant, a viralattractant, and/or in the treatment of cancer.
 77. A method of using ofan implantable device, comprising: removing a quantity of white bloodcells from a body; providing systemic chemotherapy treatment to thebody; deploying a device according to claim 72, within the body forcapturing circulating diseased cells; reintroducing the removed quantityof white blood cells into the body proximate to the device for use indegrading the captured circulating diseased cells.
 78. An implantabledevice for attracting circulating cells or foreign substancescomprising: a frame configured for positioning in a localized positionin a body vessel, at least one attractant on the frame, and at least onetherapeutic agent on the frame, wherein the attractant is capable ofattracting a diseased cell or virus and wherein the therapeutic agent iscapable of degrading the diseased cell or virus.
 79. A method ofattracting circulating cells and foreign substances, comprising:deploying in a body vessel an implantable device for attractingcirculating cells and foreign substances, the device comprising: a frameconfigured for attachment to a localized position in the body vessel,and providing at least one attractant proximate to the frame, whereinthe attractant is capable of attracting a diseased cell or foreignsubstance, said attractant optionally bound to the frame.
 80. A methodof claim 79, further comprising providing at least one therapeutic agentproximate to the frame, wherein the therapeutic agent is capable ofdegrading a diseased cell or foreign substance and, optionally, whereinthe therapeutic agent is bound to the frame.
 81. A method of claim 79,further comprising applying at least one therapeutic agent proximate tothe frame, wherein the therapeutic agent is capable of degrading adiseased cell or foreign substance.
 82. A method of claim 81, whereinthe therapeutic agent is applied by local injection.
 83. A method ofclaim 80, wherein the therapeutic agent is an ionizing radiation sourceand is directed to a location proximate to the frame.
 84. An implantabledevice according to claim 80 wherein the therapeutic agent includes anexternal energy source and is directed to a location proximate to theframe, and, optionally, wherein said external energy source isultrasound, a magnetic source or an electrical source.